(P-BT-20) Human Umbilical Cord Blood-Derived Cell Therapy in Adults with Primary Progressive Multiple Sclerosis

Background/Case Studies: Multiple Sclerosis is a multifocal demyelinating disease of the central nervous system, and the primary progressive form (PPMS) is characterized by progressive neurologic decline without periods of relapse and remission. Human Umbilical Cord Blood-Derived Cell Therapy (DUOC-01) potentially has remyelinating and immune-modulating effects, which could benefit PPMS patients. This was a single site, phase 1a, dose-escalating trial of DUOC-01 in adults with PPMS. The primary study goal was to assess the safety of a single intrathecal dose of DUOC-01 in these patients.

Study

Design/Methods: After Institutional Review Board approval and filing of an Investigational New Drug application with the Food and Drug Administration, eligible participants were administered a single intrathecal dose of DUOC-01 formulated in 5 ml of Lactated Ringers solution with 3 mg/mL of hydrocortisone after a baseline assessment with labs and MRI. A 2-week virtual visit to assess for adverse events (AEs) was followed by 3, 6, and 12-month in-person visits where physical exam, AE (coded using CTCAEv5), PPMS assessments, labs, and MRI were performed. The first 3 participants (Cohort 1) received 1.0 x 10⁷ cells, escalating to 1.1-2.5 x 10⁷ cells for the next 3 participants (Cohort 2). Due to manufacturing reliability issues, Cohort 2 was expanded to a dose of 1.1-5.0 x 10⁷ cells for 14 additional participants (Expanded Cohort 2) instead of the planned 2.5-5.0x10⁷ cells due to concerns about consistently manufacturing higher doses.

Results/Findings: 24 individuals were screened, with 3 screen failures and 2 withdrawals (1 manufacturing failure, 1 participant decision). Due to manufacturing issues, the study was terminated after 19 out of 20 planned participants received their full intended DUOC-01 dose (14 using CT-guided fluoroscopy) (Table 1). 37 AEs occurred in 12 participants, all managed with no change or supportive care. No serious AEs or HLA alloimmunizations (among 13/19 participants tested) were reported. Infusion-related AEs consisted of headache in 3 participants (2 Grade 1 and 1 Grade 2). 38 protocol deviations in 16 participants occurred. There was 1 manufacturing failure due to positive BacT with no organism identified on further testing.

Conclusions: DUOC-01 is safe for intrathecal administration in patients with PPMS. Exploratory efficacy results will be reported in the future. DUOC-01 should be further studied in the treatment of patients with MS, including PPMS, potentially receiving multiple doses.